This study will evaluate the efficacy and safety of the addition of ertugliflozin (MK-8835/PF-04971729) compared with the addition of glimepiride in participants with T2DM who have inadequate glycemic control on metformin. The duration of the trial will be up to approximately 122 weeks. This will include a 1-week screening period, an up to 13-week wash-off/titration/dose stabilization period, a 2-week placebo run-in period, a 104-week double-blind, active comparator-controlled treatment period, and a post-treatment telephone contact 14 days after the last dose of study drug. The primary hypothesis of this study is that after 52 weeks, the change from baseline in hemoglobin A1c (A1C) in participants treated with the addition of ertugliflozin 15 mg once daily is non-inferior compared with that in participants treated with the addition of glimepiride.

A Phase III, Multicenter, Randomized, Double-Blind, Active-Comparator-Controlled Clinical Trial to Study the Safety and Efficacy of the Addition of Ertugliflozin (MK-8835/PF-04971729) Compared With the Addition of Glimepiride in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin

Participants randomized to ertugliflozin 5 mg once daily (q.d.) will take one ertugliflozin 5 mg tablet, one matching placebo tablet for ertugliflozin 10 mg, and matching placebo(s) for glimepiride daily from Day 1 to Week 104.

Matching placebo to glimepiride, 1 mg or 2 mg, oral, once daily, from Day 1 to Week 104.

Drug: Metformin

Participants are to remain on their stable doses of metformin (oral, >=1500 mg/day) while receiving blinded investigational product during the double-blind treatment period. Participants on metformin <1500 at screening are up-titrated to >= 1500 daily.

Drug: Sitagliptin

Open label, oral, once daily, rescue medication as required.

Experimental: Ertugliflozin 15 mg

Participants randomized to ertugliflozin 15 mg q.d. will take one 5 mg tablet and one 10 mg tablet of ertugliflozin and matching placebo(s) for glimepiride daily from Day 1 to Week 104.

Drug: Ertugliflozin 5 mg

Ertugliflozin, 5 mg, oral, once daily, from Day 1 to Week 104

Other Name: MK-8835

Drug: Ertugliflozin 10 mg

Ertugliflozin, 10 mg, oral, once daily from Day 1 to Week 104.

Drug: Placebo to Glimepiride

Matching placebo to glimepiride, 1 mg or 2 mg, oral, once daily, from Day 1 to Week 104.

Drug: Metformin

Participants are to remain on their stable doses of metformin (oral, >=1500 mg/day) while receiving blinded investigational product during the double-blind treatment period. Participants on metformin <1500 at screening are up-titrated to >= 1500 daily.

Drug: Sitagliptin

Open label, oral, once daily, rescue medication as required.

Active Comparator: Glimepiride up to 8 mg

Participants randomized to glimepiride will take glimepiride tablets (1 and/or 2 mg) to a maximum of 8 mg and matching placebo tablets for ertugliflozin 5 mg and 10 mg daily from Day 1 to Week 104.

Drug: Glimerpiride

Glimepiride, oral tablets, initiated at 1 mg daily and titrated up to the maximum approved dose (8 mg daily based on the local country label) or maximum tolerated dose

Participants are to remain on their stable doses of metformin (oral, >=1500 mg/day) while receiving blinded investigational product during the double-blind treatment period. Participants on metformin <1500 at screening are up-titrated to >= 1500 daily.

Drug: Sitagliptin

Open label, oral, once daily, rescue medication as required.

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Diagnosis of T2DM in accordance to American Diabetes Association guidelines

On metformin monotherapy or metformin in combination with a single allowable anti-hyperglycemic agent (AHA), DPP-4 inhibitors, meglitinides and AGIs are listed as allowable AHAs along with sulfonylureas prior to study participation.

Body Mass Index (BMI) ≥18.0 kg/m^2

Male or female not of reproductive potential

If a female of reproductive potential, agree to remain abstinent or to use (or have their partner use) 2 acceptable combinations of birth control while participating in the trial and for 14 days after the last use of study drug.

Exclusion Criteria:

History or presence of type 1 diabetes mellitus or a history of ketoacidosis

History of other specific types of diabetes (eg, genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, and post-organ transplant).

A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2) inhibitor

Use of the following prohibited therapeutic agents within 12 weeks of study participation: insulin, injectable anti-hyperglycemic agents, pioglitazone or rosiglitazone, another SGLT2 inhibitor, bromocriptine (Cycloset®), colesevelam (Welchol®), and any other non-approved anti-hyperglycemic therapy

Known hypersensitivity or intolerance to metformin or glimepiride

On a weight-loss program or medication or medication associated with weight changes and is not weight-stable (>=5% change in body weight in the last 6 months)

History of bariatric surgery less than 12 months prior to study participation

Being treated for hyperthyroidism, or on thyroid replacement therapy that has not been at a stable dose for at least 6 weeks prior to study participation

Previous randomization in a study with ertugliflozin

Participation in other studies involving investigational drug(s) within 30 days of study participation and/or during the pre-randomization period

A surgical procedure within 6 weeks prior to study participation or planned major surgery during the trial

A positive urine pregnancy test

Pregnant or breast-feeding, or expecting to conceive during the trial, including 14 days following the last dose of study drug

Undergoing hormonal therapy in preparation to donate eggs during the period of the trial, including 14 days following the last dose of study drug

Consumption of more than 2 alcoholic drinks per day or engages in binge drinking

Donation of blood or blood products within 6 weeks of study participation or plans to donate blood or blood products at any time during the trial

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01999218